title: Rechallenge with mTOR inhibitors in metastatic renal cell carcinoma patients who progressed on previous mTOR inhibitor therapy.
abstract: OBJECTIVE
  To determine if mammalian target of rapamycin (mTOR) inhibitor (everolimus or temsirolimus) rechallenge in the third- or fourth-line setting after sequential use of a vascular endothelial growth factor receptor (VEGF)-targeted agent and an mTOR inhibitor is a feasible and effective treatment strategy in patients with metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  Patients who received a VEGF-targeted agent, an mTOR inhibitor and rechallenge with a second mTOR inhibitor at 2 institutions (Hôpital Européen Georges-Pompidou and Vienna Medical School) between 30 March 2001 and 15 September 2011 were included. Analyses of radiographic images were performed according to the Response Evaluation Criteria in Solid Tumors, version 1.0, to determine the objective response rate and treatment duration (TD).
  
  
  RESULTS
  Twelve patients met the inclusion criteria. Following 1 or 2 VEGF receptor-tyrosine kinase inhibitors, 7 patients firstly received everolimus and 5 patients received temsirolimus. Irrespective of treatment sequence, 6 of 12 patients (50%) responded to everolimus and 4 of 12 patients (33%) responded to temsirolimus; 3 patients (25%) did not respond to either. Median TDs (95% confidence interval) for everolimus → temsirolimus and temsirolimus → everolimus sequences were 10.3 months (8.8-19.2 months) and 5.8 months (2.9-19.3 months), respectively.
  
  
  CONCLUSIONS
  Despite the limited number of patients, this highlights the feasibility of utilizing mTOR rechallenge as an integral part of sequential treatment strategies in mRCC.
authors.affiliation: Department of Urology, Kaiser-Franz-Josef Spital, Vienna, Austria.
authors.forename: Agnes
authors.initials: A
authors.lastname: Maj-Hes
authors.forename: Jacques
authors.initials: J
authors.lastname: Medioni
authors.forename: Florian
authors.initials: F
authors.lastname: Scotte
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidinger
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.forename: Pierre
authors.initials: P
authors.lastname: Combe
authors.forename: Yohan
authors.initials: Y
authors.lastname: Gornadha
authors.forename: Reza
authors.initials: R
authors.lastname: Elaidi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus